2-azabicyclo[3.2.0]-hept-6-enes and derivatives thereof



United States Patent 3,169,972 2-AZABICYCLO[3.2.0]-HEPI-6-ENES AND DERIVATIVES THEREOF Leo A. Paquette, Portage Township, Kalamazoo County, Mich assignor to The Upjohn Company, Kalamazoo,

Mich., a corporation of Delaware No Drawing. Filed May 24, 1963, Ser. No. 282,882 10 Claims. (Cl. 260-313) and to novel 2-azabicyclo[3.2.0]heptanes of the formula:

(II) wherein R and R are alkyl of l to 4 carbon atoms, inclusive, wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, inclusive, and wherein R, is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of to carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive. R and R can be the same or different. When R is alkyl, it can be the same as or ditlerent than R R When R is alkyl, it can be the same as or different than R R or R Examples of alkyl of 1 to 4 carbon atoms, inclusive, are methyl, ethyl, propyl, butyl, and isomeric forms thereof. Examples of alkyl of 1 to 6 carbon atoms, inclusive, are methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomeric forms thereof. Examples of alkenyl of 3 to 6 carbon atoms, inclusive, are allyl, l-methylallyl, 2-methylallyl (methallyl, 2-butenyl (crotyl), 3-butenyl, 1,2 dimethylallyl, 2 ethylallyl, 1 methyl 2 butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 3-pentenyl, 2,3- dimethyl-Z-butenyl, 1,3-dimethyl-2-butenyl, l-ethyl-Z-butenyl, 4-methyl-2-pentenyl, S-hexenyl, and the like. Examples of alkynyl of 3 to 6 carbon atoms, inclusive, are 2-propynyl (propargyl), 1-methyl-2-propynyl, Z-butynyl, 3-butynyl, 1-methyI-2-butenyl, l-methyl-S-butynyl, 3 pentynyl, 1,2-dimethyl-3-butynyl, 4-pentenyl, 2-methyl-3- pentynyl, 3-hexynyl, and the like. Examples of cycloalkyl of 5 to 10 carbon atoms, inclusive, are cyclopentyl, cyclohexyl, 2-methylcyclopentyl, Z-methylcyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 2-ethylcyclopentyl, 3-ethylcyclopentyl, 3-ethylcyclohexyl, 2-propylcyclopentyl, 3-isopropylcyclopentyl, 4-propylcyclohexyl, 2,3-dimethylcyclohexyl, 2 methyl 4 ethylcyclohexyl, cycloheptyl, 3-ethylcycloheptyl, cyclo'octyl, 4-tertbutylcyclohexyl, 2,3-dimethylcyclo6ctyl, cyclononyl, cyclodecyl, and the like. Examples of aralkyl of 7 to 11 carbon atoms, inclusive, are benzyl, phenethyl, 2-phenylpropyl, 3-phenylpropyl, 4-phenylbutyl, l-naphthylmethyl, 2-naphthylmethyl, and the like.

The novel 2-azabicyclo[3.2.0]hept'6-enes and 2-aza- Lib-Pavia 3,169,972 Patented Feb. 16, 1965 bicyclo[3.2.0]heptanes of Formulas I and II, respectively, are amines and exist either in the nonprotonated (free base) form or the protonated (acid addition salt) form depending upon the pH ofv the environment. They form stable protonates, i.e., acid addition salts, on neutralization with suitable acids, for example, hydrochloric, hydrobromic, sulfuric, phosphoric, nitn'c, acetic, benzoic, salicylic, glycolic, succinic, nicotinic, tartaric, maleic, malic, pamoic, methanesulfonic, cyclohexanesulfamic, picric and latic acids, and the like. These acid addition salts are useful for upgrading the free bases. The free bases are useful as acid accep t ggs ne gtrakz iptfirfd'sirable acl'dit or in 855M551 an acid as it s fo i rn ecl in a chemical reaction, for example, a dehydrohalogenation fe'aaion in-which hydrogen and chlorine, bromine, or iodine are removed from vicinal carbon atoms.

The novel bicyclic free bases of Formulas I and H form salts with fluosilicic acid which are useful and mothproofing agents according to US. Patents 1,915,334 and 2,075,359. They also form salts with thiocyanic acid which condense with formaldehyde to form resinous materials useful as icklin inhibitors according to US. Patents 2,425,320 and 2,6j55

The Formula I and Formula 11 compounds of this invention also form salts with penicillins. These salts have solubility characteristics which cause them to be useful in the isolation and purification of penicillins, particularly benzyl penicillin. Said salts can be formed either by neutralization of the free base form of a compound of Formula I or Formula II with the free acid form of a penicillin, or by a metathetical exchange of the anion of an acid addition salt of a compound of Formula I or Formula II, for example, the chloride ion of a hydrochloride with the anionic form of a penicillin.

The novel bicyclic free bases of Formulas I and II, particularly wherein R is as defined above but not hydrogen, are useful as catalysts for reactions between isocyanates and active hydrogen compounds, e.g., alcohols and amines, and are especially useful as catalysts for the formation of polyurethanes, e.g., polyurethane foams, by interaction of polyisocyanates and polyhydroxy compounds.

2-azabicyclo[3.2.0]hept-6-enes and 2-azabicyclo[3.2.0] heptanes of Formulas I and II, respectively, are prepared by reacting the corresponding 2-azabicyclo[3.2.0]hept-6- en-3-ones and 2-azabicyclo[3.2.0]heptan-3-ones with lithium aluminum hydride, and then treating the resulting reaction mixtures with water and a base according to the following equations:

In these equations, R R R and R are as given above. 2-azab1cyclo[3.2.0]hept-6-enes of Formula I wherein R is as given above but not hydrogen are also prepared by hXAMiNtLii 3 exposing Formula V 1,3-dihydro-2H-azepines to ultraviolet radiation according to the equation:

wherein R R and R are as given above, and wherein R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of 5 to carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive. It will be noted that this definition of R excludes hydrogen but is otherwise the same as the above definition of R 2-azabicyclo[3.2.0]heptanes of Formula II wherein R is as given above but not alkenyl or alkynyl are also prepared by reduction of Formula I 2-azabicyclo[3.2.0] hept-6-enes according to the equation:

flit 1' Bl Rl R: I VII N R ultraviolet radiation O o P.

H R: R: VIII IX In this equation, R R and R are as given above.

1,3-dihydro-2H-azepin 2 ones of Formula VIII are either known in the art or can be prepared by the method known in the art, i.e., by interaction of the sodium salt of a di-ortho-substituted phenol with an ethereal solution of chloramide (ClNH preferably in the presence of an excess of the phenol [Theilacker et al., Angew. Chem. 72, 131 (1960); ibid., 75, 208-9 (1963)]. Phenols suitable for this reaction are known in the art or can be prepared by methods known in the art [e.g., US. Patents 2,831,898; 2,841,622; 2,841,623; and 2,841,624; British Patents 717,588 and 776,204; Kolka et al., J. Org. Chem. 22, 642-6 (1957) Stroh et al., Angew. Chem. 69, 699-706 (1957)]. Examples of suitable phenols are 2,6-climethylphenol (2,6-xylenol), 2,4,6-trimethylphenol (mesitol), 2, 6-diethylphenol, 2,4,6-triethylphenol, 2,6-dipropylphenol, 2,6-diisopropylphenol, 2,4,6-triisopropylphenol, 2,6-diisobutylphenol, 2,4,6-u'i-tert-butylphenol, 2-ethyl-6 methylphenol, 2-methyl-6-propylphenol, 2-ethyl-6-propylphenol, 2-tert-butyl-6-methylphenol, 2-sec-butyl-6-methylphenol, 2-tert-butyl-6-ethylphenol, 2-tert-butyl-6-isopropylphenol, 2-isobutyl-6-propylphenol, 4-sec-buty1-2,6-dimethylphenol, 4-tert-buty1-2,6-dimethylphenol, 2,4-dimethyl-6-dimethyl- 6-ethylphenol, 2,4-dimethyl-6-propyl, 6tert-butyl-2,4dimethylphenol, 2,6-diethyl-4-methylphenol, 2,6 diisopropyl-4-methylphenol, 2,4di-tert-butyl-6-methylphenol, 2,6- di-tert-butyl-4-ethylphenol, 2,4-di-tert-butyl-6-propylphenol, 2,6-diisobutyl-4-propylphenol, 2,6-di-tert-butyl-4-secbutylphenol, 2-tert-blltyl-4-ethyl 6 methylphenol, 2-secbutyl-6-isopropyl-4-methylphenol, 2-buty1-6 tert-butyl-4- methylphenol, and the like.

2-azabicyclo[3.2.0]heptan-3-ones of Formula IV wherein R is hydrogen are prepared by reduction of the corresponding Formula D( 2-azabicyc1o[3.2.0]hept-6-en-3- ones, according to the equation:

a a R1 R1 O O F, R.

R1 2 IX X In this equation, R R and R are as given above.

2-azabicyclo[3.2.0]hept-6-en-3ones and 2-azabicyclo- [3.2.0]heptan-3-ones of Formula III and IV, respectively, wherein R is as given above but not hydrogen are prepared from the corresponding Formula III and Formula IV compounds wherein R is hydrogen by replacing said hydrogen with the appropriate alkyl, alkenyl, alkynyl, cycloalkyl, or aralkyl moiety. This N-substitution is carried out in two steps according to the equations:

In these equations, R R and R are as given above; the alkali metal reactant is a material selected from the group consisting of alkali metals, alkali metal hydrides, and alkali metal amides; and R X is an organic halide wherein X is selected from the group consisting of chloride, bromide, and iodide, and wherein R is as given above.

A Formula XI 2-azabicyclo[3.2.0]hept-6-en-3-one can also be transformed by reduction to a 2-azabicyclo[3.2.0] heptan-B-one according to the equation:

1'1: 1 Br Br N N t 0 0 Pg I R; m XIII In this equation, R R R and R are as given above, and R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, inclusive, cyloalkyl of 5 to 10 carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive.

1,3-dihydro-2H-azepines of Formula V are prepared by reacting the corresponding 1,3-dihydro-2H-azepin-2- ones with lithium aluminum hydride, and then treating the resulting reaction mixtures with water and a base according to the equation:

In this equation, R R R and R are as given above.

1,3 dihydro-2H-azepin-2-ones of Formula XIV wherein R R R and R are as given above are prepared from the corresponding Formula VIII 1,3-dihydro-2H- azepin-2-ones by replacing the hydrogen attached to the nitrogen thereof with the appropriate alkyl, alkyenyl, alkynyl, cycloalkyl, or aralkyl moiety. This N-substitution is carried out in two steps according to the equation:

Alkali R metal R a a m R H Organic -11.

reaction product 0 H R: H R:

VIII XIV In this equation, R R R the alkali metal reactant, and R5X are all as defined above.

The above outlined N-substitutions of Formula D( 2- azabicyclo[3.2.0]hept-6-en-3-ones, Formula X 2-azabicyclo-[3.2.0]heptan-3-ones, and Formula VIII l,3-dihydro-ZH-azepin-Z-ones are carried out under substan tially the same reaction conditions. Examples of suitable alkali metal reactants for these reactions are lithium metal, sodium metal, potassium metal, lithium hydride, sodium hydride, potassium hydride, lithium amide, sodium amide, and potassium amide. Sodium metal, sodium hydride, and sodium amide are preferred because they are relatively inexpensive and of particularly suitable reactivity for this purpose. The alkali metal, alkali metal hydride, or alkali metal amide is preferably used in a finely divided form, preferably in admixture with or as a suspension or dispersion in an inert liquid, for example, benzene, toluene, xylene, curnene, mesitylene, tetrahydronaphthalene, hexane, heptane, octane, mineral oil, dioxane, dimethylformamide, N-methylpyrrolidone, dirnethyl sulfoxide, dialkyl ethers of ethylene glycol, dialkyl ethers of diethylene glycol, and mixtures thereof. Particularly preferred is an approximately 50 percent dispersion of micron-range sodium hydride crystals in mineral oil. An inert liquid of the type mentioned above can also with advantage be used as a solvent or diluent for the NI-I reactant, i.e., the 2-azabicyclo[3.2.0]hept-6-en-3-one, the 2-azabicyclo[3.2.0]heptan-3-one, or the 1,3-dihydro-2H-azepin-2-one reactant.

The alkali metal reactant and the N-H reactant are mixed, and the reaction between them is carried out at temperatures which can vary from about 0 to about 150 C., preferably from about 25 to about 100 C. The most suitable temperature will of course depend upon such factors as the reactivities of the alkali metal reactant and the N-H reactant, and the nature of the solvent. For example, relatively high reaction temperatures are usually necessary when using lithium reactants, and lower temperatures are preferred when using the more reactive materials such as potassium reactants. with the sodium reactants, for example, sodium hydride, reaction temperatures ranging from about 25 to about 100 C. are preferred but higher or lower temperatures can be used. It is preferred to react approximately equimolecular amounts of the N-H reactant and the alkali metal reactant, although an excess of either reactant can be used. The time required for completing the reaction will depend on the reaction temperature, the reactivities of the two reactants, and the nature of the solvent. Illustratively, with sodium hydride, the reaction usually requires about 15 minutes to about 3 hours at temperatures ranging from about 50 to about C.

After the reaction between the alkali metal reactant and the N-H reactant is complete, the mtallo-organic reaction product can be isolated from the reaction mixture, for example, by removal of the solvent by evaporation or distillation, and can be purified if desired, for example, by washing or digestion with a suitable solvent, for example, additional portions of the reaction solvent. However, where the character of the reaction mixture indicates the absence of a substantial amount of impurities, it is preferred to use the entire reaction mixture containing the metallo-organic reaction product in the next step of the reaction sequence which is a reaction with the organic halide of the formula R X, as above defined.

The organic bromides and iodides are preferred for this next step because of their greater reactivity, although the organic chlorides can be used and are advantageous in some instances because they are usually less expensive. Suitable organic bromides include methyl bromide, ethyl bromide, propyl bromide, isopropyl bromide, butyl bromide, sec-butyl bromide, isobutyl bromide, pentyl bromide, isopentyl bromide, 2-methyl-butyl bromide, 1,2- dimethylpropyl bromide, l-ethylpropyl bromide, l-methylbutyl bromide, hexyl bromide, isohexyl bromide, lmethylpentyl bromide, l-ethylbutyl bromide, Z-methylpentyl bromide, 1,2-dirnethylbutyl bromide, allyl bromide, 2 -methylallyl bromide, 2 -butenyl bromide, 3-butenyl bromide, 1,2-dimethylallyl bromide, 2-ethylallyl bromide, 1 methyl 2 butenyl bromide, 2 methyl- Z-butenyl bromide, 3-methyl-2-butenyl bromide, 2,3-dimethyl-2-butenyl bromide, 1,3-dimethyl-2-butenyl bromide, 1 ethyl 2 butenyl bromide, 4-methyl-2-pentenyl bromide, Z-propynyl bromide, Z-butynyl bromide, lmethyl-Z-propynyl bromide, 3-butynyl bromide, l-methyl- S-butynyl bromide, 3-pentynyl bromide, 4-pentynyl bromide, 3-hexynyl bromide, 2-methyl-3-pentynyl bromide, cyclopentyl bromide, cyclohexyl bromide, 2-methylcyclopentyl bromide, 2-methylcyclohexyl bromide, 3-methylcyclohexyl bromide, 4-methylcyclohexyl bromide, Z-ethylcyclopentyl bromide, 3-ethylcyclopentyl bromide, 4-ethylcyclohexyl bromide, 3-isopropylcyclopentyl bromide, 2,3- dimethylcyclohexyl bromide, cycloheptyl bromide, cyclooctyl bromide, 4-tert-butylcyclohexyl bromide, cyclononyl bromide, cyclodecyl bromide, benzyl bromide, phenethyl bromide, 2-phenyl-propyl bromide, 3-phenylpropyl bromide, 4-phenylbutyl bromide, l-naphthylmethyl bromide, Z-naphthylmethylbromide, and the like. Suitable chlorides and iodides include those corresponding to the above bromides. These halides are either known in the art or can be prepared by methods known in the art, for example, by reaction of the corresponding alcohol with a phosphorus halide, by halogenation of a suitable saturated hydrocarbon, or by addition of a hydrogen halide to a suitable unsaturated hydrocarbon.

The organic halide is added to the metallo-organic reaction mixture either dropwise or in larger portions. Alternatively, the metallo-organic reaction mixture can be added in a similar manner to the organic halide. In either case, the organic halide can be dissolved in a suitable inert solvent, preferably in one or more of the solvents already present in the metallo-organic reaction mixture. Although only one molecular equivalent of the organic halide is required for reaction with one molecular equivalent of the metallo-organic reaction product, preferably calculated on the basis of the amount of the NH reactant used to prepare the latter, it is preferred to use an excess of the organic halide, for example, about 1.01 to about 5 or even more molecular equivalents of the halide per molecular equivalent of the metallo-organic reaction product. Particularly preferred is the use of about 1.05 to about 2 molecular equivalents of organic halide per molecular equivalent of metallo-organic reaction product. Suitable reaction times and reaction temperatures for the interaction of organic halide and metallo-organic reaction product depend upon the nature of the reactants and the solvent, and the usual inverse relationship between time and temperature is observed. The organic iodides are the most reactive and the organic chlorides the least reactive. Suitable reaction temperatures range from about to about 200 C., preferably from about 10 to about 75 C. Usually, reaction temperatures ranging from about 25 to about 75 C. and reaction times ranging from about 1 to about 8 hours are satisfactory. The desired N-substituted 2-azabicyclo[3.2.0]hept-6-en-3-one, 2- azabicyclo[3.2.01heptan-3-one, or 1,3-dihydro-2H-azepin- 2-one can be isolated from the reaction mixture by conventional methods, for example, by removal of reaction solvent by evaporation or distillation. If an alkali metal halide is present as a solid in the reaction mixture, it may with advantage be removed by filtration before the desired organic reaction product is isolated.

It is preferred to use catalytic hydrogenation for the reduction of 2-azabicyclo[3.2.0]hept-6-enes (Formula I) and 2-azabicyclo[3.2.0]hept-6-en-3-ones (Formulas IX and XI) to 2-azabicyclo[3.2.0]heptanes (Formula VII) and 2-azabicyclo[3.2.0]heptan-3-ones (Formulas X and XIII), respectively. A catalyst effective to saturate a carbon-carbon double or triple bond is used. Suitable catalysts are noble metals such as platinum, palladium, rhodium, and the like, and base metals such as Raney nickel, Raney cobalt, and the like. A palladium catalyst on a carrier such as carbon or platinum oxide is usually preferred. In some hydrogenations of Formula I 2-azabicyclo[3.2.0] hept-6-enes or Formula XI 2-azabicyclo[3.2.0]hept-6-en-3- ones, however, particularly when R or R is aralkyl, e.g., benzyl, a tendency toward hydrogenolysis of the R or R moiety is observed. In such instances, hydrogenolysis is likely to be lessened by use of a rhodium catalyst rather than one of the other hydrogenation catalysts mentioned above.

The hydrogenation is preferably carried out in the presence of an inert solvent. Suitable solvents include methanol, ethanol, isopropyl alcohol, acetic acid, ethyl acetate, diethyl ether, dioxane, and the like. Hydrogenation pressures ranging from about atmospheric to about 50 psi. and hydrogenation temperatures ranging from about to about 100 C. are preferred.

The 2-azabicyclo[3.2.0]heptane or 2-azabicyclo[3.2.0] heptan 3-one product can be isolated from the hydrogenation reaction mixture by conventional techniques, for example, by filtration of the catalyst and removal of solvents by distillation. The product can be purified by conventional techniques, for example, by crystallization from a suitable solvent or mixture of solvents, by partition between two immisible solvents, by chromatography, or by a combination of these techniques. For some applications, however, it is unnecessary to purify or even to isolate the hydrogenation product. Rather, it is often satisfactory to remove the hydrogenation catalyst by filtration or centrifugation, and then use the entire solution or the crude product after removal of solvent.

This hydrogenation process is not suitable for the production of a Formula II 2-azabicyclo[3.2.0]heptane or a Formula IV 2-azabicyclo[3.2.0]heptan-3-one wherein R is alkenyl or alkynyl as above defined. Usually, the desired hydrogenation of the endocyclic 6,7-double bond is accompanied by simultaneous hydrogenation of the alkenyl or alkynyl moiety to an alkyl moiety. In these instances, if the amount of hydrogen is limited, a mixture of products is obtained. Therefore, it is preferred to use enough hydrogen to saturate both the endocyclic and exocyclic unsaturation when the reactant contains an alkenyl or alkynyl moiety.

With regard to the photoisomerization of 1,3-dihydro- 2H-azepines (Formula V) and 1,3-dihydro-2I-I-azepin-2- ones (Formula VIII) to 2-azabicyclo[3.2.0]hept-6-enes (Formula VI) and 2-azabicyclo[3.2.0]hept-6-en-3-ones (Formula IX), respectively, any source of ultraviolet radiation can be used. Compounds within the scope of Formula V generally absorb ultraviolet radiation strongly in the wave-length range 280 to 310 millimicrons. Com-- pounds within the scope of Formula VIII generally ab-- sorb strongly in the range 240 to 260 millimicrons. It is. preferred that the ultraviolet radiation used to photoisomerize Formula V compounds include the range 280 to 310 millimicrons, and that the radiation used to photoisomerize Formula VIII compounds include the range 240 to 260 millimicrons. It is not essential that other wave lengths of radiation be excluded, and therefore, either filtered or unfiltered ultraviolet radiation can be used.

The intensity of ultraviolet radiation is not critical. For example, mercury arcs with quartz envelopes and rated at 100 to 1000 watts, preferably 200 watts, are useful in these processes.

It is preferred to carry out the irradiation in the range about 20 to about 40 C., although higher or lower temperatures, for example, about 0 to about C., can be used. It is also preferred to use an inert reaction solvent, with the Formula V or Formula VIII reactant present in the concentration range about 0.1% to about 15% by weight, preferably about 0.5% to about 3% by weight. Solvents useful for this purpose include methanol, ethanol, propanol, isopropyl alcohol, benzene, toluene, hexane, chloroform, carbon tetrachloride, diethyl ether, tetrahydrofuran, and the like. Particularly preferred as solvents are methanol and tetrahydrofuran.

The length of time required for the irradiation is dependent on such factors as the nature of the reactant, the nature of the reaction solvent, the intensity of the radiation, and the temperature. For example, with a ZOO-watt mercury arc, the reaction requires about 10 to about hours at about 25 C. The course of the reaction can be followed easily by observing the gradual changes in ultraviolet absorption of the reaction mixture, particularly in the region 280 to 310 millimicrons in the case of a Formula V 1,3-dihydro-2H-azepine reactant or in the region 240 to 260 millimicrons in the case of a Formula VIII 1,3-dihydro-2H-azepin-2-one.

The Formula VI 2-azabicyclo[3.2.0] hept-6'ene product is often sensitive to oxygen and, in such instances, it is advantageous to avoid contact with air by passing a slow stream of an inert gas, for example, nitrogen or helium, through the reaction vessel during the photoisomerization. The Formula IX 2-azabicyclo[3.2.0]hept-6-en-3- one product is usually sufiiciently stable in the presence of air that there is little if any advantage in excluding air from the photoisomerization reaction vessel.

The Formula VI or Formula D( product can be isolated from the reaction mixture and purified by conventional techniques, for example, by evaporation of the solvent, followed by crystallization from a suitable solvent or mixture of solvents, by partition between two immiscible solvents, by chromatography, or by a combination of these techniques.

With regard to the reaction of lithiumrri aluminum hydride with 2-azabicyclo[3.2.0]hept-6-en-3-ones (Formula III), 2-azabicyclo[3.2.0]heptan-3-ones (Formula IV), and 1,3 dihydro 2H azepin-2-ones (Formula XIV), whereby there are obtained 2-azabicyclo[3.2.0]hept-6- enes (Formula I), 2-azabicyclo[3.2.0]heptanes (Formula II), and 1,3-dihydro-2H-azepines (Formula V), respectively, the stoichiometric amounts of reactants correspond to 0.75 mole of lithium aluminum hydride and one mole of the Formula III or IV reactant when R; in Formula III or Formula IV is hydrogen, 0.5 mole of lithium aluminum hydride and one mole of the Formula III or IV reactant when R; is as defined above but not hydrogen, and 0.5 mole of lithium aluminum hydride and one mole of the Formula XIV reactant. However, it is preferred to use an excess of lithium aluminum hydride, advantageously 50 to 300 percent excess. A larger excess can be used but there is little if any advantage in doing so.

The reactions of lithium aluminum hydride with 2- azabicyclo[3.2.0]hept 6 en 3 ones, with 2-azabicyclo [3.2.0]heptane-3-ones, and with 1,3-dihydro-2H-azepin-2- ones are carried out in substantially the same manner. Diethyl ether is preferred as a reaction solvent. Tetrahydrofuran and dibutyl ether are alternative solvents for the reactions involving 2-azabicyclo[3.2.0] heptane-3-ones. It is preferred to add a diethyl ether solution of the organic reactant to a slurry of the lithium aluminum hydride in diethyl ether, and then to reflux the resulting reaction mixture for about one to about hours, the optimum time being dependent on the nature of the organic reactant.

In the case of the 1,3-dihydro-2H-azepin-2-ones, it is important to exclude oxygen from the reaction mixture. It is also preferred to do this when using either of the other types of organic reactants. This can be accomplished by passing a slow stream of an inert gas, for example, nitrogen or helium, through the reaction vessel during the reflux period. It is also important to exclude substantial amounts of moisture from the reaction mixture. The use of dry solvents, reactants, and reaction vessels is preferred.

The first step in the isolation of the desired reaction product from the lithium aluminum hydride reaction mixture involves addition of water and a base, preferably an alkali metal hydroxide such as sodium hydroxide. Some of the desired reaction products, particularly the 1,3-dihydro-2H-azepines, decompose in the presence of substantial amounts of water, and it is preferred generally to use the minimum amount of water for this step. It is usually preferred to cool the final reaction mixture externally with ice and then to add with stirring successively about 1 m1. of water, about 1 ml. of 25 percent aqueous sodium hydroxide solution, and about 3 ml. of water for each gram of lithium aluminum hydride originally used in the reaction mixture. When these amounts of water and sodium hydroxide solution are used, the aluminate salts usually precipitate in the form of a granular solid with no separate aqueous phase. This solid precipitate is readily separated from the organic solution by filtration or centrifugation. The free base form of the desired organic product can then be isolated by evaporation of the solvent, and can be purified by conventional techniques, for example, distillation, crystallization from a suitable solvent or mixture of solvents, or chromatography.

The free base form of a 2-azabicyclo[3.2.0]hept-6-ene (Formula I) or a 2-azabicyclo[3.2.0]heptane (Formula II), prepared as described above, is transformed to an acid addition salt by neutralization with the appropriate amount of the corresponding inorganic or organic acid, examples of which are given above. These transformations can be carried out by a variety of procedures known to the art to be generally useful for the preparation of amine acid addition salts. The choice of the most suitable procedure will depend on a variety of factors including convenience of operation, economic considerations, and particularly the solubility characteristics of the Formula I or Formula II amine, the acid, and the acid addition salt. If the acid is soluble in water, the basic compound of Formula I or Formula II can be dissolved in water containing an equivalent amount of the acid, and thereafter, the water can be removed by evaporation. If the acid is soluble in a relatively non polar solvent, for example, diethyl ether or diisopropyl ether, separate solutions of the acid and the Formula I compound in such a solvent can be mixed in equivalent amounts, whereupon the acid addition salt will usually precipitate because of its relatively low solubility in the non-polar solvent. Alternatively, the basic Formula I or Formula II compound can be mixed with an equivalent amount of the acid in the presence of a solvent of moderate polarity, for example, a lower alkanol, a lower alkanone, or a lower alkyl ester of a lower alkanoic acid. Examples of these solvents are ethanol, acetone, and ethyl acetate, respectively. Subsequent admixture of the resulting solution of acid addition salt with a solvent of relatively low polarity, for example, diethyl ether or hexane, will usually cause precipitation of the acid addition salt. It is often advantageous when preparing an acid addition salt to omit isolation of the free base from its final reaction solvent, for example, the diethyl ether solution resulting from the lithium aluminum hydride reaction, or the solution remaining after catalytic hydrogenation or after ultraviolet irradiation, as described above. Rather, one of these solutions can be treated directly with the appropriate acid. The acid can be added alone or as a solution in the same or a different solvent. The acid addition salt is usually a solid and can be purified by recrystallization from a suitable solvent or mixture of solvents.

The invention can be more fully understood by the following examples.

EXAMPLE 1 1,3-dihydr0-3,5,7-trimethyI-ZH-azepin-Z-one Following the procedure of Theilacker et al., supra, the sodium salt of 2,4,6-trimethylphenol was reacted with chloramide in the presence of an excess of this phenol. 1,3-dihydro-3,5,7-trimethyl-2H-azepin-2-one was obtained; M.P. 132 C.

Following the procedure of Example 1, but substituting for the 2,4,6-trimethylphenol, 2,6-dimethylphenol; 2,6- diethylphenol; 2,6-dipropylphenol; 2,6-diisopropylphenol; 2,6-diisobutylphenol; 2,6-dibutylphenol; 2,4,6-triethylphenol; 2,6-diethyl-4-methylphenol; 2,6-dimethyl-4-ethylphenol; 4-tert-butyl 2,6 dimethylphenol; 2,6-diisopropyl-4- methylphenol; 2,6-diisobutyl-4-propylphenol; 4-sec-butyl- 2,6-dimethylphenol; and 2,4,6-triisopropylphenol, there are obtained 1,3-dihydr0-3,7-dimethyl-2H-azepin-2-one; 1,3-dihydro-3,7-diethyl-2H-azepin-2-one; 1,3-dihydro-3,7- dipropyl-2H-azepin-2-one; 1,3-dihydro 3,7 diisopropyl- 2H-azepin-2-one; 1,3 -dihydro-3 ,7-diisobutyl-2H-azepin-2- one; 1,3-dihydro- 3,7 -dibutyl-2H-azepin-2-one; 1,3-dihydro-3,5,7-triethyl-2H-azepin-2-one; l,3-dihydr0-3,7-diethyI-S-methyl-2I-l-azepin-2-one; 1,3-dihydro-3,7-dimethyl-5- ethyl-2I-I-azepin-2-one; 1,3-dihydro-5-tertbutyl-3,7-dimethyl-2H-azepin-2-one; 1,3-dihydro-3 ,7-diisopropyl-5-methyl- 2H-azepin-2-one; 1,3-dihydro-3,7-diisobutyl-5-propyl-2H- azepin-2-one; 1,3-dihydro-5-sec-butyl 3,7 dimethyl-ZH- azepin-Z-one; and 1,3-dihydro-3,5,7-triisopropyl-2H-azepin'2-one, respectively.

EXAMPLE 2 1 ,4,6-trimethyI-2-azabicyclo[3 .2 .0] hept-6-en-3-one A solution of l,3-dihydro-3,5,7-trimethyl-2H-azepin-2- one (5.0 g.; 0.033 mole) in 350 ml. of methanol was exposed to unfiltered ultraviolet radiation from a watercooled, immersion type, 200 watt, quartz Hanovia lamp for 22 hours. The temperature of the solution remained at about 20 to 25 C. during this time. The solvent was then removed by distillation and the residual brown oil was adsorbed on a 300-g. column of Florisil (60-100 mesh; a magnesium trisilicate; obtained from the Floridin Company, Tallahassee, Fla.). Elution with 4000 ml. of hexane was followed by elution with 2000 ml. of a mixture of acetone and hexane (1:10 by volume). Evaporation of the first eluate gave 1.15 g. of starting material. Evaporation of the second eluate gave 2.1 g. of a white solid which was recrystallized from hexane to give 1,4,6- trimethyl-Z-azabicyclo[3.2.0]hept-6-en-3-one; MP. 72- 73 C.

AnaIysis.-Calcd. for C H NO: C. 71.49; H, 8.67; N, 9.26. Found: C, 71.25; H, 8.36; N, 9.20.

Following the procedure of Example 2, but substituting for the 1,3-dihydro-3,5,7-trimethyl-2H-azepine-2-one, each of the 1,3-dihydro-2H-azepin-2-ones listed in Example 1, in the order listed, there are obtained distillation at reduced pressure.

1,4-dimethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 1,4-diethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 1,4-dipropyl-2-azabicyc1o[3.2.0]hept-6-en-3-one; 1,4-diisopropyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 1,4-diisobutyl-2-azabicyclo[3.2.0]hept-6-en-3-onc; 1,4-dibutyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 1,4,6-triethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; l ,4-diethyl-6-methyl-2-azabicyclo [3.2.0] hept-6-en-3-one; 1,4-dimethyl-6-ethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 6-tertbutyl-l,4-dimethyl-2-azabicyclo[3.2.0] hept-6-en-3- one; 1,4-diisopropyl-6-methyl-2-azabicyclo[3.2.0]hept-6-en-3- one; l,4-diisobutyl-6-propyl-2-azabicyclo[3.2.0]hept-6-en-3- one; 6-sec-butyl-1,4-dimethyl-2-azabicyclo[3.2.0]heptr6-en-3- one; and 1,4,6-triisopropyl-2-azabicyclo [3 .2.0] hept-6-en-3 -one, respectively.

EXAMPLE 3 I,4,6-trimethyl-2-azabicyclo[3.2.0] heptan-3-0ne A mixture of 1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6- en-3-one (9.2 g.; 0.061 mole), 100 ml. of ethanol, and 200 mg. of palladium catalyst (10% palladium on charcoal) was shaken with hydrogen at atmospheric pressure and at about 25 C. for 120 minutes. Absorption of hydrogen was about 96% of the theoretical (0.061 mole). The mixture was filtered and the solvent was removed by The crystalline residue was slurried at to C. with about ml. of hexane and filtered. The filtrate was cooled and filtered to give 7.7 g. of greyish-white blades: M.P. 94.5-96 C. Two recrystallizations from hexane gave 1,4,6-trimethyl-2- azabicyclo[3.2.0]heptan-3-one; M.P. 97.598.0 C.

Analysis.-C alcd. for C H NO: C, 70.55; H, 9.87; N, 9.14. Found: C, 70.78; H, 9.93; N, 9.33.

Following the procedure of Example 3, but substituting for the 1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-6-en-3-one,

1 ,4-dimethyl-2-azabicyclo [3 .2.0] hept-6-en-3-one; 1,4-diethyl-2-azabicyclo [3 .2.0] hept-6-en-3 -one; 1,4-diisobutyl-2-azabicyclo [3 .2.0] hept-6-en-3-one; l,4,6-triethyl-2-azabicyclo[ 3 .2.0] hept-6-en-3 -one; 1,4-dimethyl-G-ethyl-Z-azabicyclo [3 .2.0] hept-6-en-3 -one; 1,4-diisopropyl-6-methyl-2-azabicyclo [3 .2.0] hept-6-en-3- one; and 6-sec-butyl-1,4-dimethyl-2-azabicyclo [3 .2.0] hept-6-en-3- one,

there are obtained 1,4-dimethyl-2-azabicyclo [3 .2.0] heptan-3 -one; 1,4-diethyl-2-azabicyclo [3 .2.0] heptan-3 -one; 1,4-diisobutyl-2-azabicyclo[3.2.0]heptan-B-one; 1,4,6-triethyl-2-azabicyclo [3 .2.0] heptan-3 -one; 1,4-dimethyl-6-ethyl-2-azabicyclo 3 .2.0] heptan-3-one; l,4-diisopropyl-6-methyl-2-azabicyclo[3.2.0]heptan-3-one; and 6 sec-butyl-l,4-dimethyl-2-azabicyclo[3.2.0]heptan- 3-one, respectively.

EXAMPLE 4 1,2,4,6-tetramethyl-Z-azabicyclo[3.2.0] hept-6-en-3-one A 51.5% sodium hydride suspension in mineral oil (1.55 g.; equivalent to 0.033 mole of sodium hydride) was added to a solution of 1,4,6-trimethyl-2-azabicyclo[3.2.0] hept-6-en-3-one (5.0 g.; 0.033 mole) in 40 ml. of dimethylformamide. The resulting mixture was stirred and warmed to 50 C. during 30 minutes. After cooling to about 10 C., methyl iodide (4.9 g.; 0.0345 mole) was added. A precipitate formed immediately and the color of the reaction mixture changed from brown to pale yellow. The mixture was then heated with stirring at 50 C. for 30 minutes. After again cooling to about C., 50 ml. of diethyl ether was added and the precipitate was filtered. The filtrate was evaporated, and the residual 12 oil was distilled to give 3.8 g. of a colorless liquid; B.P. -110 C. at 11 mm; u 1.4835. The liquid was redistilled to give 1,2,4,6-tetramethyl-2-a2abicyclo[3.2.0] hept-6-en-3-one; B.P. -111 C. at 11 mm.; n 1.4830.

Analysis.-Calcd. for C H NO: C, 72.69; H, 9.15; N, 8.48. Found: C, 72.47; H, 8.94; N, 8.22.

Following the procedure of Example 4 but substituting for the methyl iodide, isopropyl chloride; propyl iodide; isobutyl bromide; pentyl bromide; hexyl chloride; allyl bromide; 2-methy1-2-butenyl bromide; 4-methyl-2-pentenyl chloride; 2-propynyl bromide; 3-pentynyl chloride; cyclopentyl chloride; cyclohexyl bromide; 4-tert-butylcyclohexyl chloride; benzyl bromide; and l-naphthylmethyl chloride, there are obtained 2-isopropyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6-en- 3-one; 2-propyl-l,4,6-trirnethyl-2-azabicyclo[3.2.0]hept-6-en-3- one; 2-isobutyl-l,4,6trimethyl-2-azabicyclo[3.2.0]hept-6-en-3- one; Z-pentyl-1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-6-en-3- one; 2-hexyl-1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-6-en-3- one; 2-allyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; 2-(2-methyl-2-butenyl)-1,4,6-trimethyl-Z-azabicyclo [3.2.0] hept-6-en-3-one; 2-(4-methyl-2-pentenyl)-1,4,6-trimethyl-2-azabicyclo [3.2.0]hept-6-en-3-one; 2-(2-propynyl)-1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6- en-3-one; 2-(3-pentynyl) -1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-6- en-3-one; 2-cyclopentyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6- en-3-one; 2-cyclohexyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6- en-3-one; 2-(4-tert-butylcyclohexyl)-1,4,6-trimethyl-2-azabicyclo [3.2.0]hept-6-en-3-one; 2-benzyl-1,4,6-trimethy1-2-azabicyclo[3.2.0]hept-6-en-3- one; and 2-( l-naphthylmethyl- 1 ,4,6-trimethyl-2-azabicyclo 3 .2.0]

hept-6-en-3-one, respectively.

Following the procedure of Example 4, but substituting for the combination of l,4,6-trimethyl-2-azabicyclo[3.2.0] hept-6-en-3-one and methyl iodide as reactants, 1,4-dimethyl-2-azabicyclo[3.2.0]hept-6-en-3-one plus isopropyl chloride; 1,42.d1ie$hyl-2-azabicyclo[3.2.0]hept-6-en-3-one plus ethyl 1 1 e; 1,4-dipropyl-2-azabicyclo[3.2.0]hept-6-en-3-one plus isohexyl bromide;

1,4 diisopropyl-2-azabicyclo[3.2.0]hept-6-en-3-one plus allyl bromide;

1,4-diisobutyl-2-azabicyclo[3.2.0]hept-6-en-3-one plus 5- hexenyl chloride;

1,4 dibutyl 2-azabicyclo[3.2.0]hept-6-en-3-one plus 2- butenyl bromide;

l,4,6-triethyl-2-azabicyclo[3.2.0]hept-6en-3-one plus 2- propynyl chloride;

1,4-diethyl-6-methyl-2-azabicyclo 3 .2.0] hept-6-en-3 -0ne plus 5-hexynyl chloride;

1,4-dimethyl-6-ethyl-2-azabicyclo[3.2.0]bept-6-en-3-one plus cyclopentyl chloride;

6-tert-butyl-1,4-dimethyl-2-azabicyclo[3.2.0]hept-6-en-3- one plus 4-methyl-cyclohexyl bromide;

one,

2-(2-propynyl)-1,4,6-triethyl-2-azabicyclo[3.2.0]hept-6- en-3 -one 1,4 diethyl-2-( S-hexynyl)-6-methy1-2-a2abicyclo[3.2.0]

hept-6-en-3-one;

2-cyclopentyl-1 ,4-dimethyl-6-ethyl-2-azabicyclo [3 .2.0]

hept-6-en-3-one;

6-tert-butyl-1,4-dimethyl-2-(4-methylcyclohexyl) -2-azabicyclo[3.2.0]hept-6-en-3-one;

2-benzyl-1,4-diisopropyl-6-methyl-2-azabicyclo[3.2.0]

hept-6-en-3-one; and

2-(Z-naphthylmethyl)-1,4,6-triisopropyl-2-azabicyclo [3.2.0]hept-6-en-3-one, respectively.

EXAMPLE 5 1,2,4,6-tetramethyl-2-azabicycylo[3.2.0]heptan-S-one A mixture of 1,2,4,6-tetramethyl-Z-azabicyclo[3.2.0] hept-6-en-3-one (7.0 g.; 0.042 mole), 100 ml. of absolute ethanol, and 200 mg. of palladium catalyst (10% palladium on charcoal) was shaken with hydrogen at atmospheric pressure and at about 25 C. for 120 minutes. Absorption of hydrogen ceased after 0.042 mole had been consumed. The mixture was filtered and the solvent was removed by distillation at reduced pressure. Benzene (50 ml.) was then added to the residue and the resulting solution was again evaporated to remove remaining traces of ethanol. The oily residue, 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]heptan-3-one, can be purified further by distillation but it is sufficiently pure to be used in a subsequent reaction (see Example 12).

Following the procedure of Example 5, but substituting for the respectively. In those of the above instances involving the presence of an alkenyl or alkynyl moiety in the reactant, enough hydrogen is used to saturate not only the endocyclic 6,7-double bond but also the carbon-carbon double or triple bond in the alkenyl or alkynyl moiety.

EXAMPLE 6 1,2,4,6-tetramethyl-Z-azabicyclo[3.2.0] heptan-3-one Following the procedureof Example 4, 1,4,6-trimethyl- 2-azabicyclo[3.2.0]heptan-3-one was reacted first with sodium hydride and then with methyl iodide to obtain 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]heptan-3-0ne. As in Example 5, this material need not be purified but can be used directly in a subsequent reaction (see Example 12).

Following the procedure of Example 6, but substituting for the methyl iodide, isopropyl chloride; allyl bromide; 2- propynyl chloride; cyclohexyl bromide; and benzyl bromide, there are obtained 2-isopropyl- 1,4,6-trimethyl-2-azabicyclo [3 .2.0]

heptan-3 -one;

2-allyl- 1 ,4,6-trimethyl-2-azabicyclo 3.2.0] heptan-3-one;

2-(2-propynyl)-1,4,6-trimethyl-2-azabicyclo[3.2.0]

heptan-3-one;

2-cyclohexyl-1,4,6-trimethyl-2-azabicyclo[3 .2.0]

heptan-3 -one; and

Z-benzyl-l ,4,6-trimethyl-2-azabicyclo [3 .2.0]

heptan-3-one,

respectively.

Following the procedure of Example 6, but substituting for the combination of 1,4,6-trimethyl-2-azabicyclo [3.2.0]heptan-3-one and methyl iodide as reactants, 1,4- dipropyl-2-azabicyclo[3.2.0]heptan-3-one plus isohexyl bromide; 1,4-dibutyl-2-azabicyclo[3.2.0]heptan-3-one plus 2-buteny1 bromide; 1,4-diethyl 6 methyl-Z-azabicyclo [3.2.0]heptan-3-one plus S-hexynyl chloride; 1,4-dimethyl- 6-ethyl-2-azabicyclo[3.2.0]heptan-3-one plus cyclopentyl chloride; and 1,4,6-triisopropyl-2-azabicyclo[3.2.0]heptan- 3-one plus Z-naphthylmethyl chloride, there are obtained 1,4-dipropyl-2-isohexyl-2-azabicyclo 3 .2.0] heptan-3 -one 2-(2-butenyl) -1,4-dibutyl-2-azabicyclo [3 .2.0] heptan- 3-one;

1,4-diethyl-2- S-hexynyl -6-methyl'2-azabicyclo [3 .2.0]

heptan-3-one;

2-cyclopentyl-1,4-dimethyl-6-ethyl-2-azabicyclo [3 .2.0]

heptan-3-one; and

2-(2-naphthylrnethyl)-1,4,6-triisopropyl-2-azabicyclo [3.2.0] heptan-3-one,

respectively.

EXAMPLE 7 1,3-dihydro-J,3,5,7-tetrameIhyI-ZH-azepin-Z-one A 51.5% sodium hydride suspension in mineral oil (9.0 g.; equivalent to 0.19 mole of sodium hydride) was added to a solution of 1,3-dihydro-3,5,7-trimethyl-2H-azepin-2- one (29.0 g.; 0.19 mole) in 150 ml. of dimethylformamide. The mixture was stirred at 50 C. for 1 hour. After cooling, methyl iodide (42.6 g.; 0.30 mole) was added in two portions. After stirring for 1 hour, 250 ml. of diethyl ether was added and the resulting slurry was filtered. The oil remaining after evaporation of the solvent in the filtrate was distilled to yield 29.45 g. of a colorless liquid; B.P. -120 C. at 11 mm. Redistillation gave 1,3-dihydro-1,3,5,7-tetramethyl-2H-azepin-2-one; B.P. 121.5 C. at 13 mm.; 11 1.5198.

Analysis-Caled. for C H NO: C, 72.69; H, 9.15; N, 8.48. Found: C, 72.32; H, 9.26; N, 8.59.

Following the procedure of Example 7, but substituting for the methyl iodide, isopropyl chloride; propyl iodide; isobutyl bromide; pentyl bromide; hexyl chloride; allyl bromide; 2-methyl-2-butenyl bromide; 4-methyl-2-pentenyl chloride; 2-propynyl bromide, 3-pentyny1 chloride; cyclopentyl chloride; cyclohexyl bromide; 4-tert-butylcyclohexyl chloride; benzyl bromide; and l-naphthylmethyl chloride, there are obtained 1,3-dihydro-l-isopropyl-3,5,7-trimethyl-2H-azepin-2-one; 1,B-dihydro-1-propyl-3,5,7-trimethyl-ZH-azepin-Z-one; 1,3-dihydro-1-isobutyl-3,5,7-trimethyl-2H-azepin-2-one; 1,3-dihydro-1-pentyl-3,5,7-trimethyl-2H-azepin-2-one; 1,3-dihydro-l-hexyl-3,5,7-trimethyl-2H-azepin-2-one; 1,3-dihydro-1-allyl-3,5,7-trimethyl-2H-azepin-2-one; 1,3-dihydrol-(2-methyl-2-butenyl)-3,5,7-trimethyl- 15 1,3-dihydro-l-(4-methyl-2-pentenyl)-3,5,7-trimethyl- 2H-azepin-2-one; 1,3-dihydro-1-(Z-propynyl)-3,5,7-trimethyl-2H-azepin- 2-one; l,3-dihydro-l-(3-pentynyl -3,5,7-trimethy1-2H-azepin- 2-one; 1,3-dihydro-l-cyclopentyl-3,5,7-trimethyl-2H-azepin- Z-cne; 1,3-dihydro-l-eyclohexyl-3,5,7-trimethyl-2H-azepin- 2-one; 1,3-dihydro-l-(4-tert-butylcyclohexyl)-3 ,5 ,7-trimethyl- 2H-azepin-2-one; 1,3-dihydro-1-benzyl-3,5,7-trimethyl-2H-azepin-2-one; and l,3-dihydro-l-( l-naphthylmethyl)-3,5,7-trimethyl-2H- azepin-Z-one,

respectively.

Following the procedure of Example 7, but substituting for the combination of l,3-dihydro-3,5,7-trimethyl- ZH-azepin-Z-one and methyl iodide as reactants, 1,3-dihydro-3,7-dimethyl-2H-azepin-2-one plus isopropyl chloride; 1,3-dihydro-3,7-dimethyl-2H-azepin-2-one plus cyclopentyl chloride; 1,3-dihydro-3,7-diethyl-2H-azepin-2-one plus benzyl bromide; 1,3-dihydro-3,7-diethyl-2l-I-azepin-2- one plus allyl bromide; l,3-dihydro-3,7-dipropyl-2H- azcpin-2-one plus propyl iodide; l,3-dihydro-3,7-diisopropyl-ZH-azepin-Z-one plus 4-tert-butylcyclohexyl chloride; 1,3-dihydro-3,7-diisobutyl-2H-azepin-2-one plus propyl bromide; l,3-dihydro-3,7-dibutyl-2H-azepin-2-one plus pentyl bromide; 1,3-dihydro-3,5,7-triethyl-2H-azepin-2-one plus Z-propynyl bromide; l,3-dihydro-3,7-diethyl-5- methyl-2H-azepin-2-one plus benzyl bromide; 1,3-dihydro- 3,7-dimethyl-5-ethyl-2H-azepin-2-one plus hexyl chloride; 1,3 dihydro 5 tert butyl-3,7-dimethyl-2H-azcpin-2-one plus l-naphthylmethyl chloride; l,3-dihydro-3,7-diisopropyl-S-methyl-2H-azepin-2-one plus allyl bromide; 1,3-dihydro-3,7-diisbutyl-5-propyl-2H-azepin-2-one plus propyl iodide; 1,3-dihydro--sec-butyl-3,7-dimethyl-2H- azepin-Z-one plus Z-propynyl bromide; and 1,3-dihydro- 3,5,7-triisopropyl-2H-azepin-2one plus isopropyl chloride, there are obtained 1,3-dihydro-3,7-dimethyl-l-isopropyl-ZH-azepin-Z-one; 1,3-dihydro-lcyclopentyl-3,7-dimethyl-2H-azepin-2-one; 1,S-dihydro-1-benzyl-3,7-diethyl-2H-azepin-2-one; 1,3-dihydro-l-allyl-3,7-diethyl-2H-azepin-2-one; 1,3-dihydro-l ,3,7-tripropyl-2H-azepin-2-one; 1,3-dihydro-l-(4-tert-butylcyclohexyl)-3,7-diisopropyl- 2H-azepin-2-one; l,3-dihydro-3,7-diisobutyl-l-propyl-ZH-azepin-Z-one; 1,3-dihydr-o-3,7-dibutyl-l-pentyl-2H-azepin-2-one; 1,3-dihydro-l-(2-propynyl) -3,5,7-triethyl-2H-azepin- 2-one; 1,3-dihydro-1-benzyl-3,7-diethyl-5-methyl-2H-azcpin- 2-one; 1,3-dihydro-3,7-dimethyl-5-ethyl-l-hcxyl-ZH-azepin-Z-onc; 1,34iihydro-5 -tert-butyl-3,7-dimethyl-1-( l-naphthylmethyl)-2H-azepin-2-one; 1,B-dihydro-l-ally1-3,7-diisopropyl-5-methyl-ZH-azepin- 2-one; 1,3-dihydro-3,7-diisobutyl-l,S-dipropyl-ZH-azepin-Z-one; 1,3-dihydro 5 -sec-butyl-3,7-dimethyll- Z-propynyl) -2H- azepin-Z-one; and 1 ,3 -dihydro-1 ,3,5 ,7-tetraisopropy1-2H-azepin-2-one,

respectively.

EXAMPLE 8 1,3-dihydro-1,3,5,7-tetramethyl-2H-azepine 1,3-dihydro-l,3,5,7-tetramethyl-2H-azepin-2-one (33.0 g.; 0.20 mole) was added in four portions to a stirred slurry of lithium aluminum hydride (7.6 g.; 0.20 mole) in 200 ml. of diethyl ether at about 25 C. during 10 minutes. The resulting mixture was refluxed with stirring for 3 hours while a slow stream of nitrogen gas was passed into the reaction flask. The reaction mixture was then 091l ext rnally with ice and, with continued stirring, 8 ml. of water, 8 ml. of 25% aqueous sodium hydroxide solution, and 23 ml. of water were added in that order. Stirring was continued for about 5 minutes. The granular precipitate of inorganic salts was then removed by filtration, and the filtrate was evaporated to give a pale yellow oil which was distilled under reduced pressure to give 27.7 g. of 1,3-dihydro-1,3,5,7-tetramethyl- ZH-azepine in the form of a colorless liquid which rapidly turned yellow; B.P. -54 C. at 1.0 mm.

U.V. (diethyl ether) 301 mp (5:7,050). LR. (principal bands; CCl; solution) 1635 and 1595 cmf EXAMPLE 9 1,3-dihydro-1-ethyl-3,5,7-trimeIhyI-ZH-azepine Following the procedure of Example 8, 1,3-dihydro 1-ethyl-3,5,7-trimethyl-2H-azepin-2-one (7.7 g.; 0.043 mole) was reacted with lithium aluminum hydride (1.6 g.; 0.043 mole) to give 5.6 g. of l,3-dihydro-l-ethyl-3,5,7- trimethyl-ZH-azepine in the form of a colorless liquid which slowly turned yellow; B.P. til-64 C. at 1 mm.; n 1.5176.

U.V. (diethyl ether) 305 mu (e=7,500). LR. (principal bands; CCl solution) 1635 and 1585 cm.-

Following the procedure of Example 8, but substituting for the 1,3'dihydro-l,3,5,7-tetramethyl-2H-azepin-2-one,

1,3-dihydro-l-allyl-3,5,7-t:rimethyl-2H-azepin-2-one; 1,3-dihydro-l-cyclopentyl-3,5,7-trimethyl-2H-azepin- 2-one; l,3-dihydro-l-benzyl-3,7-diethyl-2H-azepin-2-one; 1,3-dihydro-1-(4-tert-butylcyclohexyl)-3,7-diisopropyl- 2H-azepin-2-one; l,3-dihydro-3,7-dipropyl-1-hexyl-2H-azepin-2-one; and 1,3-dihydro-1-(2-propynyl)-3,5,7-triethyl-2H-aaepin-2-one,

there are obtained 1,3-dihydro- 1-a1lyl-3 ,5 ,7-trimethyl-2H-azepine; 1,3-dihydro-l-cyclopentyl-3,5 ,7-trimethyl-2H-azaepine; l;3-dihydro-l-benzyl-3,7-diethyl-2H-azepine; 1,3-dihydro-1-(4-tert-butylcyclohexyl)-3,7-diisopropyl-2H- azepine; 1,3-dihydno-3,7dipropyl-l-hexyl-ZH-azepine; and 1,3-dihydro-1-(2-propynyl) -3,5,7-triethyl-2H-azepine, respectively.

EXAMPLE 10 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]hept-6-ene -A solution of 1,3-dihydro-l,3,5,7-tetramethyl-2H-azepine (20.0 g.; 0.13 mole) in 400 ml. of dry peroxide-free tetrahydrofuran was exposed to unfiltered ultraviolet radiation from a water-cooled, immersion type, 200 watt quartz Hanovia lamp for 72 hours. Air was excluded by passing a slow stream of nitrogen gas through the reaction flask during the irradiation period. The solvent was then evaporated and the residual liquid was distilled to give 16.1 g. of 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]hept-6- ene in the form of a colorless liquid; B.P. 28 C. at 1 mm.; 21 1.4568. A portion of thi material was mixed with ethanolic picric acid to give the picric acid addition salt of l,2,4,6-tetramethyl-2-azabicyclo[3.2.0]hept-6-ene; M.P. 212-214 C. after recrystallization from ethanol.

01 C 5H oN4Oq: C, 50.52; H, N, 14.73. Found: C, 50.48; H, 4.93; N, 14.63.

Addition of ethanolic solutions of hydrogen chloride, sulfuric acid, phosphoric acid, benzoic acid, and salicylic acid to ethanolic solutions of 1,2,4,6-tctramethyl-2-azabicyclo-[3.2.0]hept-6-ene, followed by addition of several volumes of diethyl ether, gave the corresponding hydrochloric, sulfuric, phosphoric, benzoic, and salicylic acid addition salts.

Following the procedure of Example 10, but substituting for the 1,3-dihydro-1,3,5,7-tetramethyl-2H-azepine,

1,3-dihydro-1-allyl-3,5,7-trimcthyl-2H-azepine;

17 1,B-dihydro-l-benzy1-3,7-diethyl-2H-azepine; 1,3-dihydro-1-(4-tert-butylcyclohexyl) -3 ,7-diisopropyl- 2H-azepine; 1,3-dihydro-3,7-dipropyl-l-hexyl-ZH-azepine; and 1,3-dihydro-1-(2-propynyl)-3,5,7-triethyl-2H-azepine, 5 there are obtained respectively.

EXAMPLE 11 1 ,2,4,6-tetramethyl-Z-azabicyclo [3 .2 .0] heptane A mixture of 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]- hept-6-ene (2.0 g.; 0.013 mole), 50 ml. of ethanol, and 200 mg. of platinum oxide was shaken with hydrogen at atmospheric pressure and at about C. for 120 minutes. Absorption of hydrogen ceased after 0.013 mole had been consumed. The mixture was filtered and to the filtrate was added a slight excess of hydrogen chloride dissolved in diethyl ether. Evaporation of solvents under reduced pressure gave an oil which crystallized after addition of about 5 ml. of diethyl ether and cooling at 5 C. for about 15 hours. This material was filtered and dried to give 1.4 g. of pink solid; M.P. 187-192 C. Recrystallization from a mixture of ethanol and diethyl ether gave 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]heptane hydrochloride, with substantially the same infrared spectrum as the hydrochloride of Example 12.

Analysis.Calcd. for CIOHZOCIN: C, 63.30; H, 10.63; N, 7.38. Found: C, 63.61; H, 10.87; N, 7.15.

Addition of the above hydrochloride to aqueous sodium hydroxide solution, followed by extraction with diethyl ether, drying of the ether extract, and evaporation of the ether gave 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]- heptane free base.

When ethereal solutions of sulfuric acid, phosphoric acid, benzoic acid, and salicylic acid are used in place of ethereal hydrogen chloride, the corresponding sulfuric, phosphoric, benzoic, and salicylic acid addition salts of 1,2,4,6-tetra.methyl 2-azabicyclo[3.2.0]heptane are obtained.

Following the procedure of Example 11, but substituting for the 1,2,4,6-tetramethyl2-azabicyclo [3 .2.0] hept-6-ene, 1,4,6-trimethyl-2-azabicyclo 3 .2.0] hept-6-ene; 1,4-diethyl-2-azabicyclo 3 .2.0] hept-6-ene; 6-tert-butyl-1,4-dimethyl-2-azabicyclo[3.2.0]l1ept-6-ene; 2-cyclopenty1- 1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept- 6-ene; 2-(4-tert-butylcyclohexyl) -1,4-diisopropyl-2-azabicyclo- [3.2.0]hept-6-ene; 1,4-dipropyl-2-hexyl-2-azabicyclo 3 .2 .0] hept-6-ene; 2-allyll ,4,6-trimethyl-2-azabicyclo 3 .2.0] hept-6-ene; and 2-(2-propyny1) -1,4,6-triethyl-2-azabicyclo [3.2.0]hept- 6-ene, there are obtained 1,4,6-trimethyl-2 azabicyclo 3 .2.0] heptane; 1,4-diethyl-2-azabicyclo 3 .2.0] heptane; 6-tert-butyll ,4-dimethyl-2-azabicyclo 3 .2.0] heptane; 2-cyclopentyl-1,4,6-trimethyl-2-azabicyclo [3.2.0]

heptane; 2-(4-tert-butylcyclohexyl) -1,4-diisopropyl-2- azabicyclo [3 .2.0] heptane; 1,4-dipropyl-2-hexyl-2-azabicyclo [3.2.0] heptane; 2-propyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]heptane; and 2-pr0pyl-1 ,4,6-triethyl-2-azabicyclo [3 .2.0] heptane,

respectively. For the preparation of the latter two products, enough hydrogen is used to saturate not only the 75 6,7-double bond but also the carbon-carbon double or triple bond in the alkenyl or alkynyl moiety. In each reduction the free base is obtained in solution and is transformed to the hydrochloride by addition of ethereal hydrogen chloride. When addition of ethereal hydrogen chloride is omitted and the solvent is evaporated from the final free base solution, said free base is obtained and is purified by distillation at reduced pressure. When ethereal solutions of sulfuric, phosphoric, benzoic, or salicylic acids are used in place of ethereal hydrogen chloride, the corresponding sulfuric, phosphoric, benzoic, or salicylic acid addition salts are obtained.

EXAMPLE 12 I ,2,4,6-tetramethy l-2-azabicyclo [3 .2.0] heptane The residual oil obtained in Example 5 by catalytic hydrogenation of 1,2,4,6-tetramethyl-2-azabicyc1o[3.2.0]- hept-6-en-3-one (7.0 g.; 0.042 mole) was dissolved in 25 ml. of diethyl ether, and was added gradually during 10 minutes to a stirred slurry of lithium aluminum hydride (1.9 g.; 0.05 mole) in ml. of diethyl ether. The resulting mixture was refluxed with stirring for 2 hours while a slow stream of nitrogen gas was passed into the reaction flask. The reaction mixture was then cooled externally with ice and, with continued stirring, 2 ml. of water, 2 ml. of 25% aqueous sodium hydroxide solution, and 6 ml. of water were added in that order. Stirring was continued for about 5 minutes. The granular precipitate of aluminate salts was then removed by filtration, and to the filtrate was added an ethereal hydrogen chloride solution until fresh additions no longer resulted in the formation of additional precipitate. This precipitate was filtered, washed with diethyl ether, and dried to give 7.3 g. of white solid; MP. 204205 C. Recrystallization from a mixture of ethanol and diethyl ether gave 1,2,4,6-tetramethyl-2 azabicyclo[3.2.0]heptane hydrochloride in the form of a white solid, M.P. 213.5- 215 C.

AnaIysis.Calcd. for C H ClN: C, 63.30; H, 10.63; N, 7.38. Found: C, 63.70; H, 10.46; N, 7.41.

Addition of the above hydrochloride to aqueous sodium hydroxide solution, followed by extraction with diethyl ether, drying of the ether extract, and evaporation of the ether gave 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0] heptane free base.

Following the procedure of Example 12, but substituting for the crude 1,2,4,6-tetramethyl-2-azabicyclo [3 .2.0] heptan-3-one,

either a similarly crude form or a purified form of 1,4,6-trimethyl-2-azabicyclo[3.2.0]heptan-3-one; 1 ,4-diethyl-2-azabicyclo [3 .2.0] heptan-3-one; 6-tert-butyl-1,4-dimethyl-2-azabicyclo[3.2.0]heptan-3- one; 2-isopropyl-1,4,6-trimethyl-2-azabicyclo[3.2.0]

heptan-3-one; 2-allyl-1,4,6-trimethyl-2-azabicyclo 3.2.0] heptan-3-one; 1,4dipropyl-Z-isohexyl-Z-azabicyclo[3.2.0] heptan-3-one; 2-cyclopentyl-1,4-dimethyl-6-ethyl-2-azabicyclo- [3.2.0]heptan-3-one; 2-(2-naphthylmethyl)-1,4,6-triisopropyl-2-azabicyc1o- [3.2.0]heptane-3-one; and 2-(2-propynyl)-1,4,6-trimethyl-2-azabicyclo- [3.2.0]heptan-3-one, there are obtained 1,4,6-trimethyl-2-azabicyclo[3.2.0]heptane; 1,4-diethyl-2-azabicyclo[3.2.0]heptane; 6-tert-butyl-1,4-dimethyl-2-azabicyclo[3.2.0]heptane; 2-isopropyl-1,4,6-trimethyl-2-azabicyclo [3 .2.0] heptane; 2-al1yl-1,4,6-trimethyl-2-azabicyclo[3.2.0]heptane; 1,4-dipropyl-2-isohexyl-2-azabicyclo 3.2.0] heptane; 2-cyclopentyl-1,4-dimethyl-6-ethyl-2-azabicyclo- [3.2.0]heptane; 2-(Z-naphthylmethyl)-1,4,6-triisopropyl-2-azabicyclo- [3.2.0]heptane; and 2-(2-propynyl) -1,4,6-trimethyl-2-azabicyclo- [3.2.0]heptane, respectively, both as the free base and as the hydrochloride.

in the case of the above preparation of 1,2,4,6-tetramethyl-Z-azabicyclo[3.2.0]heptane as well as in the preparation of any of the other specific 2-azabicyclo[3.2.0]- heptanes mentioned above, when the ethereal solution of hydrogen chloride is replaced with an equivalent amount of an ethereal solution of sulfuric acid, phosporic acid, benzoic acid, or salicylic acid, the corresponding acid addition salts are obtained.

EXAMPLE 13 1,2,4,6-tetramethyl-Z-azabicyclo[3.2.0]hept-6-ene Following the procedure of Example 12, but substituting for the crude l,2,4,6-tetramethyl-2-azabicyclo- [3.2.0]heptan 3 one, 1,2,4,6 tetramethyl 2 azabicyclo[3.2.0]hept-6-en-3-one, there were obtained both the hydrochloride and the free base form of l,2,4,6- tetramethyl 2 azabicyclo[3.2.0]hept 6 ene. The picric acid addition salt was also made by the procedure of Example 10. This free base and its picrate had substantially the same physical characteristics as the free base and picrate described in Example 10.

When ethereal solutions of sulfuric acid, phosphoric acid, benzoic acid, and salicylic acid are used in place of ethereal hydrogen chloride, the corresponding sulfuric, phosphoric, benzoic, and salicylic acid addition salts of 1,2,4,6 tetramethyl 2 azabicyc1o[3.2.0]hept 6 ene are obtained.

Following the procedure of Example 13, but substituting for the 1,2,4,6-tetramethyl-2-azabicyclo[3.2.0]hept- 6-en-3-one, l,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6-en-3-one; l,4 diethyl-2-azabicyclo 3.2.0] hept-6-en-3-one; 6-tert-butyl-1,4-dimethyl-2-azabicyclo [3 .2 .0] hept-6-en- 3-one; 2-isopropyl-l,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6- en-3-one; 2-allyl-l,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6-en- 3-one; 2-benzyl-1,4,6-t.rimethyl-2-azabicyclo[3.2.0]hept-6-en- 3-one; l,4-dipropyl-2-isohexyl-2-azabicyclo [3.2.0] hept-6-en- 3-one; 2-(2-butenyl)-l,4-dibutyl-2-azabicyclo[3.2.0]hept-6- en-3-one; 2-cyclopenty1-1,4-dimethyl-6-ethyl-2-azabicyclo[3.2.0]-

hept-6-en-3-one; 2-(2-naphthylmethyl)-l,4,6-triisopropyl-2-azabicyclo[3.2.0]hept-6-en-3-one; and 2-(2-propynyl)-1,4,6-triethyl-2-azabicyclo[3.2.0]hept- 6-en-3-one; there are obtained 1,4,6-trimethy1-2-azabicyclo[3.2.0]hept-6-ene; 1,4-diethyl-2-azabicyclo [3 .2.0] hept-6-ene 6-tert-butyl-l,4-dimethyl-2-azabicyclo[3.2.0]hept-6-ene; 2-isopropyl-l,4,6-trimethyl-2-azabicyclo[3.2.0]hept-6-ene; 2-a.-lly1-1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-G-ene; 2-benzyl-1,4,6-trimethyl-2-azabicyclo [3 .2.0] hept-6 -ene 1,4-dipropyl-2-isohexyl-2-azabicyclo[3.2.0.]hept-6-ene; 1H 2-butenyl) -l ,4-dibutyl-2-azabicyclo [3.2.0]hept-6-ene 2-cyclopentyl-1,4-dimethyl-6-ethyl-2-azabicyclo[3.2.0]-

hept-6-ene; 2-(2-naphthylmethyl)-1,4,6-triisopropyl-2-azabicyclo[3.2.0]hept-6-ene; and 2-(2-propynyl) -1,4,6-triethyl-2-azabicyclo[3 .2.0] hept- 6-ene, respectively, both as the tree base and as the hydro chloride.

When the ethereal solution of hydrogen chloride used to make the hydrochloride of each of the above 2-azabicyclo[3.2.0]hept-6-enes is replaced with ethereal solutions of sulfuric acid, phosphoric acid, benzoic acid, and salicylic acid, the corresponding acid addition salts are obtained.

wherein R and R are alkyl of 1 to 4 carbon atoms, inclusive, wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, inclusive, and wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of 5 to 10 carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive.

2. l,2,4,6-tetramethyl-2-azabicyclo[3.2.0]hept-6-ene.

3. 1,2,4,6 tetramethyl 2 azabicyclo[3.2.0]hept 6- ene hydrochloride.

4. A compound selected from the group consisting of the free base form and acid addition salts of a compound of the formula:

wherein R and R are alkyl of 1 to 4 carbon atoms, inclusive, wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, inclusive, and wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of 5 to 10 carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive.

5. 1,2,4,6-tetramethyl-2-azabicyc1o[3.2.0]heptane.

6. 1,2,4,6 tetramethyl 2 azabicyclo[3.2.0]heptane picric acid addition salt.

7. A process for producing a 2-azabicyclo[3.2.0]hept- 6-ene of the formula:

wherein R and R are alkyl of 1 to 4 carbon atoms, inclusive, wherein R is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, inclusive, and wherein R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of 5 to 10 carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive, which comprises exposing a compound of the formula:

7 wherein R R R and R are as given above, to ultraviolet radiation, to form said 2-azabicyclo[3.2.0]hept 6-ene.

8. The process of claim 7 wherein the wave length of said ultraviolet radiation includes the range 280 to 310 millimicrons.

9. A process for producing a 2-azabicyclo[3.2.0]heptane of the formula:

wherein R R and R are as given above, and wherein R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, inclusive, alkenyl of 3 to 6 carbon atoms, inclusive, alkynyl of 3 to 6 carbon atoms, inclusive, cycloalkyl of 5 to 10 carbon atoms, inclusive, and aralkyl of 7 to 11 carbon atoms, inclusive, to ultraviolet radiation, and (2) mixing the organic product from step (1) with hydrogen in the presence of a hydrogenation catalyst, to form said 2-azabicyclo[3.2.0]heptane.

10. The process of claim 9 wherein the wave length of said ultarviolet radiation includes the range 280 to 310 millimicrons.

OTHER REFERENCES Cram et al.: Organic Chemistry, McGraw-Hill Book Co., Inc., New York, 1959, pages 74 and 353.

NICHOLAS S. RIZZO, Primary Examiner. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF THE FREE BASE FORM AND ACID ADDITION SALTS OF A COMPOUND OF THE FORMULA:
 7. A PROCESS FOR PRODUCING A 2-AZABICYCLO(3.2.1)HEPT6-ENE OF THE FORMULA: 